The catechol estrogens, 2 or 4 hydroxyderivatives of estrone and estradiol, represent major metabolites of the naturally occurring estrogens. Little is known about the origin, disposition, and metabolic effects of these compounds. The objective of this project is to answer these questions. Progress to date reveals the catechol estrogens to be weak estrogen agonists, the 4-hydroxy compounds being stronger than the 2 hydroxy isomers, with no evidence of estrogen antagonist activity. Themetabolic clearance of these compounds is extremely rapid, more than 20,000 L/day, and they appear to serve primarily as deactivated metabolites of estrone and estradiol.